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| Mutations in the chloride channel gene, CLCNKB, cause Bartter's syndrome type III |
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| Author(s): Simon DB, Bindra RS, Mansfield TA, NelsonWilliams C, Mendonca E, Stone R, Schurman S, Nayir A, Alpay H, Bakkaloglu A, RodriguezSoriano J, Morales JM, Sanjad SA, Taylor CM, Pilz D, Brem A, Trachtman H, Griswold W, Richard GA, John E, Lifton RP |
| Source: NATURE GENETICS Volume: 17 Issue: 2 Pages: 171-178 Published: OCT 1997 |
| Times Cited: 416 References: 28 |
| Abstract: Analysis of patients with inherited hypokalaemic alkalosis resulting from salt-wasting has proved fertile ground for identification of essential elements of renal salt homeostasis and blood-pressure regulation. We now demonstrate linkage of this phenotype to a segment of chromosome 1 containing the gene encoding a renal chloride channel, CLCNKB. Examination of this gene reveals loss-of-function mutations that impair renal chloride reabsorption in the thick ascending limb of Henle's loop. Mutations in seventeen kindreds have been identified, and they include large deletions and nonsense and missense mutations. Some of the deletions are shown to have arisen by unequal crossing over between CLCNKB and the nearby related gene, CLCNKA. Patients who harbour CLCNKB mutations are characterized by hypokalaemic alkalosis with salt-wasting, low blood pressure, normal magnesium and hyper-or normocalciuria; they define a distinct subset of patients with Bartter's syndrome in whom nephrocalcinosis is absent. These findings demonstrate the critical role of CLCNKB in renal salt reabsorption and blood-pressure homeostasis, and demonstrate the potential role of specific CLCNKB antagonists as diuretic antihypertensive agents. |
| Document Type: Article |
| Language: English |
Addresses:
1. YALE UNIV, SCH MED, HOWARD HUGHES MED INST, DEPT MED, BOYER CTR MOL MED, NEW HAVEN, CT 06510 USA
2. YALE UNIV, SCH MED, HOWARD HUGHES MED INST, DEPT GENET, BOYER CTR MOL MED, NEW HAVEN, CT 06510 USA
3. HOSP SANTA MARIA, UNIDADE NEFROL PEDIAT, LISBON, PORTUGAL
4. UNIV S FLORIDA, ALL CHILDRENS HOSP, DEPT PEDIAT, ST PETERSBURG, FL 33701 USA
5. UNIV ISTANBUL, DEPT PEDIAT NEPHROL, ISTANBUL, TURKEY
6. HACETTEPE UNIV, CHILDRENS HOSP, DEPT PEDIAT NEPHROL, ANKARA, TURKEY
7. HOSP CRUCES, DEPT PEDIAT, BARACALDO, SPAIN
8. HOSP UNIV 12 OCTUBRE, DEPT MED, MADRID, SPAIN
9. KING FAISAL SPECIALIST HOSP & RES CTR, DEPT PEDIAT, RIYADH 11211, SAUDI ARABIA
10. CHILDRENS HOSP, DEPT NEPHROL, BIRMINGHAM B16 8ET, W MIDLANDS ENGLAND
11. UNIV WALES HOSP, INST MED GENET, CARDIFF CF4 4XW, S GLAM WALES
12. RHODE ISL HOSP, DEPT PEDIAT NEPHROL, PROVIDENCE, RI 02903 USA
13. SCHNEIDER CHILDRENS HOSP, ALBERT EINSTEIN COLL MED, DEPT PEDIAT, NEW HYDE PK, NY 11040 USA
14. CHILDRENS HOSP SAN DIEGO, DEPT PEDIAT, SAN DIEGO, CA 92123 USA
15. UNIV FLORIDA, DEPT PEDIAT, GAINESVILLE, FL 32610 USA
16. UNIV ILLINOIS, DEPT PEDIAT, CHICAGO, IL 60612 USA |
| Publisher: NATURE PUBLISHING CO, 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 |
| Subject Category: Genetics & Heredity |
| IDS Number: XZ555 |
| ISSN: 1061-4036 |
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